Our overall goal to define the natural history, complications, and risk factors associated with recurrent genital HSV infection remains the same. Prospective studies have shown that the recurrence rates of genital HSV-1 and oropharyngeal HSV-2 are 8-10 times less than genital HSV-2 and oral HSV-1, respectively. Young age, and the recent acquisition of genital herpes increase the frequency of asymptomatic genital HSV infection and host response to several HSV polypeptides (gD and VP16) influence the frequency and severity of recurrent disease. In addition, 25% of women enrolled after first episode genital herpes have developed CIN within 2 years. Women with asymptomatic HSV infection developed CIN significantly sooner (mean 782 days) than women who did not (mean 1,263 days, p=.04). In planned studies, we will continue to explore factors associated with recurrences of disease, focus on the natural history of asymptomatic genital herpes and expand our efforts at evaluating the effects of genital herpes on pregnancy morbidity. We will continue follow-up of our current cohort of patients after first episode genital herpes to evaluate whether symptomatic and/or asymptomatic genital HSV infection changes in frequency over time. Detailed colposcopic, histologic, and DNA hybridization studies to investigate the frequency of concomitant human papillomavirus (HPV) infection in genital HSV patients and the relationship between HPV, HSV and CIN will be performed. Collaborative studies will be conducted to correlate the serological and local immune responses to specific viral polypeptides including epitopes to these proteins (gD-1, gD-2, gG and VP16) with the frequency of reactivation and the maintenance of latency. We will initiate studies of the natural history, of asymptomatic genital herpes in lower and middle socioeconomic males and females and continue investigations defining the transmission of infection. In pregnant women, we will conduct a series of collaborative studies to define the role of HSV in prematurity, the frequency of asymptomatic genital HSV infection at term and risk factors associated with transmission of infection to the neonate.